TY - JOUR
T1 - Nivolumab plus ipilimumab versus sunitinib in previously untreated advanced renal-cell carcinoma
T2 - Analysis of Japanese patients in CheckMate 214 with extended follow-up
AU - Tomita, Yoshihiko
AU - Kondo, Tsunenori
AU - Kimura, Go
AU - Inoue, Takamitsu
AU - Wakumoto, Yoshiaki
AU - Yao, Masahiro
AU - Sugiyama, Takayuki
AU - Oya, Mototsugu
AU - Fujii, Yasuhisa
AU - Obara, Wataru
AU - Motzer, Robert J.
AU - Uemura, Hirotsugu
N1 - Funding Information:
This work was supported by Bristol-Myers Squibb and ONO Pharmaceutical Company Ltd. Patients treated at Memorial Sloan Kettering Cancer Center were supported in part by Memorial Sloan Kettering Cancer Center Support Grant/Core Grant [P30 CA008748]. Authors received no financial support or compensation for publication of this manuscript.
Funding Information:
We thank the patients and their families for making this study possible. We also acknowledge the contributions of Sabeen Mekan, MD (formerly of Bristol-Myers Squibb) to the original data analyses and early development of the manuscript. Professional medical writing and editorial assistance were provided by Juan Sanchez-Cortes, PhD, and Lawrence Hargett of Parexel, funded by Bristol-Myers Squibb.
Funding Information:
Yoshihiko Tomita reports research funding from Astellas, AstraZeneca, ONO Pharmaceutical Company Ltd., Pfizer, and Chugai; honoraria from Astellas, Bristol-Myers Squibb, Novartis, and Pfizer; and consultancy fees from Novartis, ONO Pharmaceutical Company Ltd., and Taiho Pharmaceutical Company Ltd. Tsunenori Kondo reports honorarium from ONO Pharmaceutical Company Ltd. Go Kimura reports consultancy fees from Novartis, ONO Pharmaceutical Company Ltd., Bristol-Myers Squibb, Pfizer, and Bayer. Takamitsu Inoue has no conflicts of interest to report. Yoshiaki Wakumoto has no conflicts of interest to report. Masahiro Yao reports research funding from ONO Pharmaceutical Company Ltd. Takayuki Sugiyama has no conflicts of interest to report. Mototsugu Oya reports honoraria from ONO Pharmaceutical Company Ltd., Bristol-Myers Squibb, Pfizer, Bayer, and Novartis. Yasuhisa Fujii has no conflicts of interest to report. Wataru Obara reports departmental funding from Bristol-Myers Squibb. Robert J. Motzer has received research funding paid to employer and consultancy fees from Bristol-Myers Squibb, Pfizer, Novartis, Eisai, Exelixis, and Genentech/Roche, and consultancy fees from Merck, Incyte, and Lilly. Hirotsugu Uemura has received honoraria from Bayer, Janssen, Astellas, Pfizer, AstraZeneca, Takeda Pharmaceutical Company Ltd., Sanofi, Bristol-Myers Squibb, and MSD; research funding from Janssen, Astellas, Pfizer, AstraZeneca, Takeda, Taiho, ONO Pharmaceutical Company, Ltd., and Sanofi; consultancy/advisory fees from Bayer, MSD, Janssen, Bristol-Myers Squibb, ONO Pharmaceutical Company Ltd., and Sanofi; and has been a study investigator for Bayer, MSD, Janssen, Bristol-Myers Squibb, ONO Pharmaceutical Company Ltd., Novartis, Astellas, Pfizer, and Chugai Pharmaceutical Co. Ltd. M. Brent McHenry reports personal fees from stock ownership of and is an employee of Bristol-Myers Squibb.
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2019/12/23
Y1 - 2019/12/23
N2 - Background: Nivolumab plus ipilimumab (NIVO+IPI) demonstrated superior efficacy over sunitinib (SUN) for previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 214, with a manageable safety profile. We report efficacy and safety with extended follow-up amongst Japanese patients. Methods: CheckMate 214 patients received NIVO (3 mg/kg) plus IPI (1 mg/kg) every 3 weeks for four doses, then NIVO (3 mg/kg) every 2 weeks; or SUN (50 mg) once daily for 4 weeks (6-week cycle). This subgroup analysis assessed overall survival (OS), objective response rate (ORR) and progression-free survival (PFS) per investigator in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk and intent-To-Treat (ITT) patients and safety (ITT patients). Results: Of 550 and 546 patients randomized to NIVO+IPI and SUN, 38 and 34, respectively, were Japanese. Of these, 31 (NIVO+IPI) and 29 (SUN) patients were IMDC intermediate/poor-risk. In IMDC intermediate/poor-risk patients with 30 months' minimum follow-up, there was a delayed trend in OS benefit with NIVO+IPI (hazard ratio [HR] 0.56; 95% confidence interval [CI]: 0.19-1.59; P = 0.2670), and 24-month OS probability favoured NIVO+IPI (84%) versus SUN (76%). The ORR was 39% with NIVO+IPI and 31% with SUN (P = 0.6968). PFS was similar in both treatment arms (HR 1.17; 95% CI: 0.62-2.20; P = 0.6220). Efficacy in ITT patients was similar to IMDC intermediate/poor-risk patients. Grade 3-4 treatment-related adverse event incidence was lower with NIVO+IPI versus SUN (58 versus 91%). Conclusions: Japanese patients with untreated aRCC in the NIVO+IPI arm had a numerically higher ORR and improved safety profile versus patients in the SUN arm. A delayed OS benefit appears to be emerging with NIVO+IPI. Longer follow-up is needed. https://clinicaltrials.gov/ct2/show/NCT02231749?term=NCT02231749&rank=1 identifier: NCT02231749.
AB - Background: Nivolumab plus ipilimumab (NIVO+IPI) demonstrated superior efficacy over sunitinib (SUN) for previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 214, with a manageable safety profile. We report efficacy and safety with extended follow-up amongst Japanese patients. Methods: CheckMate 214 patients received NIVO (3 mg/kg) plus IPI (1 mg/kg) every 3 weeks for four doses, then NIVO (3 mg/kg) every 2 weeks; or SUN (50 mg) once daily for 4 weeks (6-week cycle). This subgroup analysis assessed overall survival (OS), objective response rate (ORR) and progression-free survival (PFS) per investigator in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk and intent-To-Treat (ITT) patients and safety (ITT patients). Results: Of 550 and 546 patients randomized to NIVO+IPI and SUN, 38 and 34, respectively, were Japanese. Of these, 31 (NIVO+IPI) and 29 (SUN) patients were IMDC intermediate/poor-risk. In IMDC intermediate/poor-risk patients with 30 months' minimum follow-up, there was a delayed trend in OS benefit with NIVO+IPI (hazard ratio [HR] 0.56; 95% confidence interval [CI]: 0.19-1.59; P = 0.2670), and 24-month OS probability favoured NIVO+IPI (84%) versus SUN (76%). The ORR was 39% with NIVO+IPI and 31% with SUN (P = 0.6968). PFS was similar in both treatment arms (HR 1.17; 95% CI: 0.62-2.20; P = 0.6220). Efficacy in ITT patients was similar to IMDC intermediate/poor-risk patients. Grade 3-4 treatment-related adverse event incidence was lower with NIVO+IPI versus SUN (58 versus 91%). Conclusions: Japanese patients with untreated aRCC in the NIVO+IPI arm had a numerically higher ORR and improved safety profile versus patients in the SUN arm. A delayed OS benefit appears to be emerging with NIVO+IPI. Longer follow-up is needed. https://clinicaltrials.gov/ct2/show/NCT02231749?term=NCT02231749&rank=1 identifier: NCT02231749.
KW - Japanese
KW - advanced renal cell carcinoma
KW - first-line treatment
KW - ipilimumab
KW - nivolumab
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U2 - 10.1093/jjco/hyz132
DO - 10.1093/jjco/hyz132
M3 - Article
C2 - 31633185
AN - SCOPUS:85076811868
VL - 50
SP - 12
EP - 19
JO - Japanese Journal of Clinical Oncology
JF - Japanese Journal of Clinical Oncology
SN - 0368-2811
IS - 1
ER -
